Examples of glucose sensors dealing with a sample of whole blood include sensors that utilize a colorimetric method or an electrode method (see Patent Documents 1 and 2, for example). In both of the above-described two techniques, the glucose level is determined by supplying electrons taken from glucose to an electron detection medium (color former or electrode) and grasping, from the outside of the glucose sensor, the amount of electrons supplied. Generally, the glucose sensor is designed to take electrons from glucose by oxidoreductase and supplying the electrons to the electron detection medium via an electron mediator.
It is known that, in measuring the glucose level using whole blood, the measurement result is influenced by the blood cell concentration (hematocrit), and a high hematocrit causes the measurement result to be lower than the actual glucose level. As one of the causes of such a phenomenon, it has been pointed out that to take electrons from the glucose existing in blood cells requires longer time than to take electrons from the glucose existing in blood serum (blood plasma). Specifically, electrons can be quickly taken from the glucose existing in blood serum (blood plasma) by oxidoreductase. On the other hand, electrons existing in the glucose in blood cells cannot be taken out until the glucose is transferred to the blood serum (blood plasma). Further, the transfer of glucose from blood cells to blood serum (blood plasma) is not the simple diffusion due to the difference of glucose level between inside and outside of blood cells but the facilitated diffusion which depends on the glucose transmission ability of blood cell membranes. Thus, the rate of diffusion of glucose to the outside of blood cells follows the Michaelis-Menten equation and has a limit value. Therefore, when the difference of glucose level between inside and outside of the blood cells exceeds a predetermined value, the rate of diffusion of glucose to the outside of blood cells becomes a constant value. Therefore, in a system in whole blood in which an oxidoreductase, an electron mediator and an electron detection medium coexist, although electrons taken from the glucose existing in blood serum (blood plasma) are immediately supplied to the electron detection medium, it takes time to diffuse the glucose of the amount corresponding to the supplied amount to the outside of the blood cells. As a result, the electrons taken from the glucose originally existed in blood cells are supplied to the electron detection medium later as compared with the glucose originally existed in the blood serum (blood plasma). Such a delay is large in the whole blood with high blood cell concentration. Therefore, in a stage after a certain period has elapsed from the sample supply, the ratio of glucose transferred from blood cells to blood serum (blood plasma) may be smaller in the whole blood having a high blood cell concentration than in the whole blood having a low blood cell concentration even when the blood glucose level is the same.
Recently, the measurement time tends to be shortened, and novel oxidoreductase and electron mediator are sought for the purpose. In such a condition, the glucose existing in the blood serum (blood plasma) is consumed in a short time. On the other hand, the rate of transfer of glucose from blood cells does not change greatly, because the diffusion of glucose from the blood cells to the blood serum (blood plasma) depends on the glucose transmission ability of blood cell membranes. Therefore, in whole blood with high hematocrit, as the measurement time is shortened, the ratio of glucose which can be transferred from blood cells to blood serum (blood plasma) within the measurement time decreases, and the above-mentioned low-value problem becomes more significant.
Moreover, the oxidoreductase and the electron mediator are retained in the glucose sensor as a reagent portion in a solid state soluble in blood, for example (See Patent Document 3, for example). Therefore, as the measurement time is shortened, the influence of the solubility of the reagent portion on the measurement accuracy increases. When the reagent portion has poor solubility, the oxidoreductase and the electron mediator do not disperse uniformly in the liquid phase reaction system established when the reagent portion is dissolved by the blood, which causes variations in the measurement results. Such variations in the measurement results are remarkable when the glucose level in the blood is low.
Patent Document 1: JP-A-2002-175699
Patent Document 2: JP-B-8-10208
Patent Document 3: JP-A-2004-101519